Morphine-induced mydriasis and fluctuation in the rat: time and dose relationships

The purpose of this investigation was to establish complete dose- and time-response relationships of morphine action on the rat pupil using serial observations. Adult male, albino rats of the Sprague-Dawley strain were used. Pupil size was measured by a series of photographs taken every 60 sec for at least 90 min under dim red illumination. The pupil began to dilate within 20 min after s.c. administration of doses of morphine sulfate as low as 1 mg/kg. The dose-related mydriasis reached a maximum with a dose of 32 mg/kg at 35 to 50 min after injection and lasted for 3 to 4 hr. The mydriasis was characterized by a rapid and marked fluctuation which was also dose-related and reached a peak with 32 mg/kg of morphine sulfate. Naloxone HCl (1 mg/kg) rapidly reversed both the mydriasis and the oscillation, thereby implicating an opiate receptor-mediated mechanism. In addition to providing a convenient measure of narcotic actions, the pupil may offer a particularly useful means for studying opiate receptor mechanisms since it is one of the few cases where, in many species, the anatomical pathways and neurochemical innervations are known.